Potassium Carbonate → HCID 178502289, compound

HRID 1751542Notes

Reaction equation

HRID 1751542 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:12][C:11]([C@@H:13]3[CH2:21][C:16]4([O:20][CH2:19][CH2:18][O:17]4)[CH2:15][N:14]3[C:22](=[O:32])[C@@H:23]([NH:27][C:28](=[O:31])[O:29][CH3:30])[CH:24]([CH3:26])[CH3:25])=[N:10][CH:9]=2)=[CH:4][CH:3]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].Br[C:57]1[CH:58]=[C:59]2[C:79](=[CH:80][CH:81]=1)[C:63]1[NH:64][C:65]([C@@H:67]3[CH2:71][CH2:70][CH2:69][N:68]3[C:72]([O:74][C:75]([CH3:78])([CH3:77])[CH3:76])=[O:73])=[N:66][C:62]=1[CH:61]=[CH:60]2.C([O-])([O-])=O.[K+].[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCOCC1.CS(C)=O>[CH3:30][O:29][C:28]([NH:27][C@@H:23]([CH:24]([CH3:26])[CH3:25])[C:22]([N:14]1[C@H:13]([C:11]2[NH:12][C:8]([C:5]3[CH:6]=[CH:7][C:2]([C:57]4[CH:58]=[C:59]5[C:79](=[CH:80][CH:81]=4)[C:63]4[NH:64][C:65]([C@@H:67]6[CH2:71][CH2:70][CH2:69][N:68]6[C:72]([O:74][C:75]([CH3:77])([CH3:78])[CH3:76])=[O:73])=[N:66][C:62]=4[CH:61]=[CH:60]5)=[CH:3][CH:4]=3)=[CH:9][N:10]=2)[CH2:21][C:16]2([O:20][CH2:19][CH2:18][O:17]2)[CH2:15]1)=[O:32])=[O:31]

Participants

10

Reactant 5

HCID 11430Potassium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 59610362((S)-1-{(S)-8-[4-(4-Bromo-phenyl)-1H-imidazol-2-yl]-1,4-dioxa-7-aza-spiro[4.4]nonane-7-carbonyl}-2-methyl-propyl)-carbamic acid methyl esterHCID 178451893(S)-tert-butyl 2-(7-bromo-1H-naphtho[1,2-d]imidazol-2-yl)pyrrolidine-1-carboxylate

Product 1

HCID 178502289HCID 178502289, compound

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 679Dimethyl SulfoxideSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
95 °C

Procedure

Methyl (S)-1-((S)-8-(5-(4-bromophenyl)-1H-imidazol-2-yl)-1,4-dioxa-7-azaspiro[4.4]nonan-7-yl)-3-methyl-1-oxobutan-2-ylcarbamate (100 mg, 0.197 mmol), bis(pinacolato)diboron (51 mg, 0.2 mmol), potassium acetate (58 mg, 0.591 mmol), and Pd(dppf)Cl2 (15 mg, 0.02 mmol) were all weighed out in a glass pressure vessel and anhydrous 1,4-Dioxane (1 mL) was added. The mixture was bubbled with nitrogen gas for about 5 min. The vessel was then capped and sealed and heated in an oil bath at 95° C. overnight with continuous stirring. The reaction vessel was cooled down to room temperature and (S)-tert-butyl 2-(7-bromo-1H-naphtho[1,2-d]imidazol-2-yl)pyrrolidine-1-carboxylate (83 mg, 0.29 mmol), 2M K2CO3 (296 uL), and Pd(PPh3)4 (23 mg, 0.02 mmol) were all added along with 1 mL of DMSO or 1,4-dioxane and the mixture was bubbled with nitrogen gas for 5 minutes. The vessel, again, was capped, sealed and placed in an oil bath at 100° C. for 4 hours.

Workup

  1. customall weighed out in a glass pressure vessel
  2. customThe mixture was bubbled with nitrogen gas for about 5 min
  3. customThe vessel was then capped
  4. customsealed
  5. temperatureThe reaction vessel was cooled down to room temperature
  6. customthe mixture was bubbled with nitrogen gas for 5 minutes
  7. customThe vessel, again, was capped
  8. customsealed

Sources & evidence

ORD record
ord-9b1feda1d8cd4818bb823c600e5cf309
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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